Thymosin alpha 1 exerts beneficial extrapulmonary effects in cystic fibrosis

Marina M. Bellet, Monica Borghi, Marilena Pariano, Giorgia Renga, Claudia Stincardini, Fiorella D'Onofrio, Stefano Brancorsini, Enrico Garaci, Claudio Costantini, Luigina Romani

Research output: Contribution to journalArticlepeer-review

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding for the ion channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Long considered a lung disease for the devastating impact on the respiratory function, the recent diagnostic and therapeutic advances have shed the light on the extra-pulmonary manifestations of CF, including gastrointestinal, hepatobiliary and pancreatic symptoms. We have previously demonstrated that thymosin alpha1 (Tα1), a naturally occurring immunomodulatory peptide, displays multi-sided beneficial effects in CF that concur in ameliorating the lung inflammatory pathology. In the present study, by resorting to murine models of gut inflammation with clinical relevance for CF patients, we demonstrate that Tα1 can also have beneficial effects in extrapulmonary pathology. Specifically, Tα1 restored barrier integrity and immune homeostasis in the inflamed gut of CF mice as well as in mice with the metabolic syndrome, a disorder that may arise in CF patients with high caloric intake despite pancreatic sufficiency. The protective effects of Tα1 also extended to pancreas and liver, further emphasizing the beneficial effects of Tα1 in extra-pulmonary complications of CF. By performing wide-ranging multi-organ anti-inflammatory effects, Tα1 could potentially integrate current therapeutic approaches to tackle the complex symptomatology of CF disease.

Original languageEnglish
Article number112921
JournalEuropean Journal of Medicinal Chemistry
Volume209
DOIs
Publication statusPublished - Jan 1 2021

Keywords

  • Candida albicans
  • Cystic fibrosis
  • Diet-induced obesity
  • IDO1
  • Intestinal inflammation

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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